Despite evidence of adverse health effects resulting from exposure to welding fume and in particular to manganese (Mn), biomarkers of exposure are poorly understood and have not been thoroughly evaluated in a longitudinal design. This study is designed to evaluate the relationship between well-characterized inhaled Mn exposure and a number of short- and long-term biomarkers of Mn exposure. We will recruit a cohort of 80 apprentice welders and intensively evaluate airborne Mn concentrations and biomarkers of Mn exposure among members of the cohort over four weeks of intensive exposure, and then again four weeks after exposure cessation. Personal airborne exposures to Mn and other components of welding fume will be measured twice weekly on each participating subject during the exposure period. In addition, the particle size distribution of Mn and total welding fume particulate will be evaluated to determine its influence on exposure biomarkers. Short-term biomarkers of exposure to be evaluated in all subjects are blood Mn and urine Mn. Long-term biomarkers of exposure which will be assessed among a subset of 20 subjects are hair Mn and two measures of Mn concentration in brain tissue, the Pallidal Index (PI) and T1 relaxation time, evaluated via magnetic resonance imaging (MRI). Biomarkers of biological effect will also be evaluated among all subjects for comparison with the exposure indices. Clinical motor function tests (UDPRS3 and Purdue Pegboard test) will be administered to subjects undergoing MRI evaluation to allow for exploration of the relationship between biomarkers of Mn exposure in brain tissue and motor task performance. Individual characteristics with the potential to influence the relationship between air and biomarker concentrations, including diet, smoking status, and pre-existing health conditions, will be assessed in all subjects via questionnaire. We will model the relationships between air exposure levels and exposure biomarkers using a mixed effects distributed lag model to allow for description and testing of the contribution of recent and cumulative exposure on each observed biomarker. Relationships between air or biomarker-based exposures and biomarkers of effect will be similarly modeled. The results will inform future epidemiological exposure assessment in studies of welding or Mn- related health effects and provide guidance on interpretation of Mn biomarker results in a variety of exposure contexts. PUBLIC HEALTH RELEVANCE: Although there is evidence that occupational exposure to inhaled manganese results in adverse health effects, biomarkers of exposure to manganese are poorly understood. This study will explore the relationships between airborne manganese concentrations and a variety of biomarkers of manganese exposure, including blood, urine, hair, and brain tissue (assessed via magnetic resonance imaging), over time in a group of apprentice welders.